Document Detail


A novel ETA-receptor antagonist, FR 139317, inhibits endothelin-induced contractions of guinea-pig pulmonary arteries, but not trachea.
MedLine Citation:
PMID:  8448595     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. The effects of a proposed endothelin-receptor antagonist, FR 139317, on the contraction induced by endothelin-1, endothelin-2 and endothelin-3, were analysed on isolated circular segments of pulmonary arteries and rings of trachea from the guinea-pig. 2. The pharmacological profiles of endothelin-1 and endothelin-2 were almost identical in the guinea-pig pulmonary artery, whereas endothelin-3 demonstrated a weaker and less potent contractile effect. The contractions induced by endothelin-1 and endotheliln-2 were competitively antagonized by FR 139317. Schild plot analysis revealed a straight line with a slope that did not differ from unity. The pA2 value was 6.65. In contrast, the endothelin-3 induced contractile response was unaffected by FR 139317. 3. In tracheal segments endothelin-1, endothelin-2 and endothelin-3 evoked contractions of similar magnitude and sensitivity. FR 139317 had no effect on the endothelin-induced contractions in tracheal segments. 4. In ring segments of pulmonary artery and trachea, potassium, noradrenaline and histamine caused concentration-dependent contractile effects. These contractions were not modified by FR 139317 in the concentration range 10(-7) to 3 x 10(-6)M. 5. FR 139317 seems to be a selective ETA-receptor antagonist which competitively antagonizes the endothelin-1- and endothelin-2-induced contractions of guinea-pig isolated pulmonary arteries. Thus, the guinea-pig pulmonary artery appears to be endowed with one receptor type (ETA) which is antagonized by FR 139317 and with another endothelin-receptor subtype which responds to endothelin-3, but is not antagonized by FR 139317. In the trachea, all three peptides act on a homogeneous population of receptors which is unaffected by FR 139317. This suggests an ETA-receptor in the guinea-pig pulmonary artery and another receptor, probably of ETB-type, in the guinea-pig trachea.
Authors:
L O Cardell; R Uddman; L Edvinsson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  108     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1993 Feb 
Date Detail:
Created Date:  1993-04-09     Completed Date:  1993-04-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  448-52     Citation Subset:  IM    
Affiliation:
Department of Otorhinolaryngology, Malmö General Hospital, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Azepines / pharmacology*
Guinea Pigs
Indoles / pharmacology*
Male
Muscle, Smooth / drug effects*
Pulmonary Artery / drug effects
Receptors, Endothelin / antagonists & inhibitors*
Trachea / drug effects
Vasoconstriction / drug effects*
Chemical
Reg. No./Substance:
0/Azepines; 0/Indoles; 0/Receptors, Endothelin; 142375-60-8/FR 139317
Comments/Corrections

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